Defect of MLH1 expression sensitized esophageal squamous cell carcinoma cells to Polθ inhibitor

BACKGROUND: A large scale detection of MLH1 methylation is lacking in esophageal cancer. MLH1 is a well-known mismatch repair gene. The mechanism of MLH1 in DNA double strand break (DSB) repair remains unclear. METHODS: Esophageal cancer cell lines and 1018 cases of primary cancer samples were employed. Methylation specific PCR, Western Blot, and CRISPR/Cas9 knockout technique were utilized. RESULTS: < 0.05). MLH1 promotes ataxia telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR), and non-homologous end-joining repair (NHEJ), while inhibiting microhomology-mediated end joining (MMEJ) repair signaling pathways. Deletion of MLH1 sensitized esophageal cancer cells to novobiocin. CONCLUSIONS: MLH1 plays important roles in DSB repair and deletion of MLH1 sensitizes ESCC cells to Polθ inhibitor.